Glioblastoma-related gene mutations and over-expression of functional epidermal growth factor receptors in SKMG-3 glioma cells

C. Thomas, G. Ely, C. D. James, Robert Brian Jenkins, M. Kastan, A. Jedlicka, P. Burger, R. Wharen

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Amplification of the epidermal growth factor receptor (EGFR) gene is found in about 40% of glioblastomas (GBMs) but is rarely detected in GBM cell lines. We confirmed that the exceptional SKMG-3 GBM cell line retained amplified EGFR genes in vitro, and found that these sequences were concentrated on extra-chromosomal DNA particles similar to double-minute chromosomes. The cells contained two other gene mutations that are associated with high-grade astrocytic tumors: extra-chromosomal amplification of the cyclin-dependent kinase-4 (CDK4) gene and a homozygous mutation within the PTEN tumor suppressor gene. Immunoblots revealed very high levels of EGFR, moderately increased expression of CDK4, and no detectable PTEN protein. The over-expressed SKMG-3 EGFRs responded to exogenous ligand and resembled normal rather than mutant receptors. A heterozygous mutation of the p53 gene (p53R282W) correlated with failure of radiation to induce the expression of cyclin-dependent kinase inhibitor p21waf1 or an early G1 cell cycle arrest. Although each of these gene mutations occurs in GBMs, SKMG-3 cells had an unusual genotype in that a p53 gene mutation co-existed with amplified EGFR genes. Nonetheless, the SKMG-3 cell line can be exploited as a model to study how oncogenic EGFR signals in GBM cells interact with over-expressed CDK4 and loss of PTEN to confer the malignant phenotype.

Original languageEnglish (US)
Pages (from-to)605-615
Number of pages11
JournalActa Neuropathologica
Volume101
Issue number6
StatePublished - 2001

Fingerprint

Glioblastoma
Glioma
Cyclin-Dependent Kinase 4
erbB-1 Genes
Mutation
Genes
p53 Genes
Epidermal Growth Factor Receptor
Cell Line
PTEN Phosphohydrolase
G1 Phase Cell Cycle Checkpoints
Cyclin-Dependent Kinases
Tumor Suppressor Genes
Chromosomes
Genotype
ErbB Receptors
Radiation
Ligands
Phenotype
DNA

Keywords

  • Epidermal growth factor receptor
  • Glioblastoma
  • p53 gene
  • PTEN
  • Tumor cells

ASJC Scopus subject areas

  • Clinical Neurology
  • Pathology and Forensic Medicine
  • Neuroscience(all)

Cite this

Glioblastoma-related gene mutations and over-expression of functional epidermal growth factor receptors in SKMG-3 glioma cells. / Thomas, C.; Ely, G.; James, C. D.; Jenkins, Robert Brian; Kastan, M.; Jedlicka, A.; Burger, P.; Wharen, R.

In: Acta Neuropathologica, Vol. 101, No. 6, 2001, p. 605-615.

Research output: Contribution to journalArticle

Thomas, C, Ely, G, James, CD, Jenkins, RB, Kastan, M, Jedlicka, A, Burger, P & Wharen, R 2001, 'Glioblastoma-related gene mutations and over-expression of functional epidermal growth factor receptors in SKMG-3 glioma cells', Acta Neuropathologica, vol. 101, no. 6, pp. 605-615.
Thomas, C. ; Ely, G. ; James, C. D. ; Jenkins, Robert Brian ; Kastan, M. ; Jedlicka, A. ; Burger, P. ; Wharen, R. / Glioblastoma-related gene mutations and over-expression of functional epidermal growth factor receptors in SKMG-3 glioma cells. In: Acta Neuropathologica. 2001 ; Vol. 101, No. 6. pp. 605-615.
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